Shen K-Z, Johnson S W
Department of Neurology, Oregon Health and Science University, Portland, OR 97239, USA.
Neuroscience. 2008 Feb 19;151(4):1029-33. doi: 10.1016/j.neuroscience.2007.12.001. Epub 2007 Dec 8.
The subthalamic nucleus (STN) plays a pivotal role in normal and abnormal motor function. We used patch pipettes to study effects of 5-HT on synaptic currents evoked in STN neurons by focal electrical stimulation of rat brain slices. 5-HT (10 microM) reduced glutamate-mediated excitatory postsynaptic currents (EPSCs) by 35+/-4%. However, a much higher concentration of 5-HT (100 microM) was required to inhibit GABA-mediated inhibitory postsynaptic currents (IPSCs) to a comparable extent. Concentration-response curves showed that the 5-HT inhibitory concentration 50% (IC50) for inhibition of IPSCs (20.2 microM) was more than fivefold greater than the IC50 for inhibition of EPSCs (3.4 microM). The 5-HT-induced reductions in EPSCs and IPSCs were accompanied by increases in paired-pulse ratios, indicating that 5-HT acts presynaptically to inhibit synaptic transmission. The 5-HT1B receptor antagonist NAS-181 significantly antagonized 5-HT-induced inhibitions of EPSCs and IPSCs. These studies show that 5-HT inhibits synaptic transmission in the STN by activating presynaptic 5-HT1B receptors.
丘脑底核(STN)在正常和异常运动功能中起关键作用。我们使用膜片吸管研究了5-羟色胺(5-HT)对大鼠脑片局灶性电刺激诱发的STN神经元突触电流的影响。5-羟色胺(10微摩尔)使谷氨酸介导的兴奋性突触后电流(EPSCs)降低了35±4%。然而,需要更高浓度的5-羟色胺(100微摩尔)才能将γ-氨基丁酸(GABA)介导的抑制性突触后电流(IPSCs)抑制到相当的程度。浓度-反应曲线表明,5-羟色胺抑制IPSCs的半数抑制浓度(IC50)(20.2微摩尔)比抑制EPSCs的IC50(3.4微摩尔)高五倍多。5-羟色胺诱导的EPSCs和IPSCs的降低伴随着配对脉冲比率的增加,表明5-羟色胺在突触前起作用以抑制突触传递。5-羟色胺1B受体拮抗剂NAS-181显著拮抗5-羟色胺诱导的对EPSCs和IPSCs的抑制作用。这些研究表明,5-羟色胺通过激活突触前5-羟色胺1B受体抑制STN中的突触传递。